Is RECQL4 p.Ala337Pro (c.1009G>C) pathogenic?

RECQL4 p.Ala337Pro (c.1009G>C) is classified Uncertain significance in RECQL4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-22). AlphaMissense: likely benign (0.0837); Very rare (popmax 0.00133%, afr); Associated with Inborn genetic diseases.

What condition is associated with RECQL4 p.Ala337Pro (c.1009G>C)?

RECQL4 p.Ala337Pro (c.1009G>C) is associated with Inborn genetic diseases, Baller-Gerold syndrome (ClinVar).

How common is RECQL4 p.Ala337Pro (c.1009G>C) in the general population?

RECQL4 p.Ala337Pro (c.1009G>C) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about RECQL4 p.Ala337Pro (c.1009G>C)?

AlphaMissense predicts likely benign (score 0.0837) — an in-silico prediction, not a clinical call.

RECQL4 p.Ala337Pro

c.1009G>C · rs1171953080 · VCV575295

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0837 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0837	likely benign
SaProt	LLR -6.15	tolerated
⇒ AlphaMissense and SaProt both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.95	GERP -3.2
Regional constraint	o/e 1.39	unconstrained · MANE · 6,350 bp · p 1.8e-56 · regional, not allelic
Overall
CADD	0.267	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; SaProt is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,924 alleles

Overall 6.2e-05% 1/1,612,764 alleles · very rare exomes 0/1,460,538 · genomes 1/152,226 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: RECQL4
Protein: p.Ala337Pro
Coding: c.1009G>C
MANE Select: NM_004260
dbSNP: rs1171953080
Type: single nucleotide variant
Location: chr8:144516110 (GRCh38)
Gene constraint: LOEUF 1.519 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.32 · 2 PDB

Full RECQL4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Baller-Gerold syndrome

Similar variants

RECQL4 p.Ala337Asp Uncertain significance ★★ ⚠ same residue
RECQL4 p.Ala337Gly Uncertain significance ★★ ⚠ same residue
RECQL4 p.Ala337Val Uncertain significance ★★ ⚠ same residue
RECQL4 p.Ala337Ser Uncertain significance ★ ⚠ same residue
RECQL4 p.Ala337= Likely benign ★ same residue
RECQL4 p.Ala337fs Pathogenic ★ same residue
RECQL4 c.1132-1G>A Likely pathogenic ★★ same condition
RECQL4 c.1259-1G>A Pathogenic/Likely pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/recql4-p-ala337pro (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown